P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver

Kamochi, Masayuki; Kamochi, F.; Kim, Y. B.; Sawh, Seema; Sanders, John M.; Sarembock, Ian J.; Green, S.; Young, Jeffrey S.; Ley, Klaus; Fu, Shu Man; Rose, Charles E.

doi:10.1152/ajplung.1999.277.2.l310

Cited by 73 publications

(78 citation statements)

References 47 publications

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“…Infiltration of various tissues such as liver, lung, and kidney by neutrophils and other inflammatory leukocytes has been well demonstrated to occur after LPS administration (21,29,30). LPS, as well as cytokines such as TNF, are known to up-regulate chemotactic chemokines and adhesion molecules, such as ICAM-1, which promote leukocyte adhesion and migration (19 -21).…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Cunningham

Wang

Guo

et al. 2004

The Journal of Immunology

227

186

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Toll-like receptor 4 (TLR4) is present on monocytes and other cell types, and mediates inflammatory events such as the release of TNF after exposure to LPS. C3H/HeJ mice are resistant to LPS-induced mortality, due to a naturally occurring mutation in TLR4. We therefore hypothesized that LPS-induced acute renal failure (ARF) requires systemic TNF release triggered by LPS acting on extrarenal TLR4. We injected C3H/HeJ mice and C3H/HeOuJ controls with 0.25 mg of LPS, and sacrificed them 6 h later for analysis of blood urea nitrogen (BUN) and kidney tissue (n = 8 per group). In contrast to C3H/HeOuJ controls, C3H/HeJ mice were completely resistant to LPS-induced ARF (6-h BUN of 32.3 ± 1.1 vs 61.7 ± 5.6 mg/dl). C3H/HeJ mice released no TNF into the circulation at 2 h (0.00 vs 1.24 ± 0.16 ng/ml), had less renal neutrophil infiltration (6.4 ± 1.0 vs 11.4 ± 1.3 neutrophils per high power field), and less renal apoptosis, as assessed by DNA laddering. Transplant studies showed that C3H/HeJ recipients of wild-type kidneys (n = 9) were protected from LPS-induced ARF, while wild-type recipients of C3H/HeJ kidneys (n = 11) developed severe LPS-induced ARF (24-h BUN 44.0 ± 4.1 vs 112.1 ± 20.0 mg/dl). These experiments support our hypothesis that LPS acts on extrarenal TLR4, thereby leading to systemic TNF release and subsequent ARF. Renal neutrophil infiltration and renal cell apoptosis are potential mechanisms by which endotoxemia leads to functional ARF.

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Section: Discussionmentioning

confidence: 99%

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Cunningham

Wang

Guo

et al. 2004

The Journal of Immunology

227

186

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“…ICAM-1 is an important adhesion molecule in neutrophil recruitment and extravasation through endothelial cells in inflammatory sites and has been implicated in liver injury models such as endotoxic shock and ischemia/reperfusion-induced liver injury. 14,29,30 Upregulated expression of ICAM-1 in the liver has been reported in APAP hepatotoxicity. 10 To examine whether ICAM-1 plays a role in the neutrophil accumulation in APAPtreated mice, experiments were carried out in ICAM-1-deficient mice.…”

Section: Increased Infiltration Of Neutrophils In the Livermentioning

confidence: 99%

Neutrophil depletion protects against murine acetaminophen hepatotoxicity

et al. 2006

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We previously reported that liver natural killer (NK) and NKT cells play a critical role in mouse model of acetaminophen (APAP)-induced liver injury by producing interferon gamma (IFN-␥) and modulating chemokine production and subsequent recruitment of neutrophils into the liver. In this report, we examined the role of neutrophils in the progression of APAP hepatotoxicity. C57BL/6 mice were given an intraperitoneal toxic dose of APAP (500 mg/kg), which caused severe acute liver injury characterized by significant elevation of serum ALT, centrilobular hepatic necrosis, and increased hepatic inflammatory cell accumulation. Flow cytometric analysis of isolated hepatic leukocytes demonstrated that the major fraction of increased hepatic leukocytes at 6 and 24 hours after APAP was neutrophils (Mac-1 ؉ Gr-1 ؉ ). Depletion of neutrophils by in vivo treatment with anti-Gr-1 antibody (RB6-8C5) significantly protected mice against APAP-induced liver injury, as evidenced by markedly reduced serum ALT levels, centrilobular hepatic necrosis, and improved mouse survival. The protection was associated with decreased FasL-expressing cells, cytotoxicity against hepatocytes, and respiratory burst in hepatic leukocytes. In intracellular adhesion molecule (ICAM)-1-deficient mice, APAP caused markedly reduced liver injury when compared with wild-type mice. The marked protection in ICAM-1-deficient mice was associated with decreased accumulation of neutrophils in the liver. Hepatic GSH depletion and APAP-adducts showed no differences among the antibody-treated, ICAM-1-deficient, and normal mice. In conclusion, accumulated neutrophils in the liver contribute to the progression and severity of APAP-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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“…Blood was collected for Ig measurements by incision of the axillary artery. BAL collection and lung fixation were performed essentially as previously described (20). Briefly, a 22-gauge catheter was inserted into the exposed trachea of exsanguinated mice and secured with ligatures.…”

Section: Bal and Lung Histologymentioning

confidence: 99%

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Sung

Rose

2001

The Journal of Immunology

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Dendritic cells (DC) are the primary APC responsible for the capture of allergens in the airways and the shuttling of processed allergens to the draining lymph nodes where Ag presentation and T cell activation take place. The mechanism of this Ag handling and presentation in asthma is poorly understood. In addition, the feasibility of asthma induction by DC priming has not been directly tested. In this report an asthma model using intratracheally (i.t.) injected splenic DC was used to address these issues. DC pulsed with a model Ag OVA or the major MHC class II-restricted OVA T epitope peptide OVA323–339 and instilled i.t. primed mice to exhibit asthma-like diseases. With OVA as the Ag, mice exhibit airway hyperresponsiveness (AHR), lung eosinophilia and inflammation, and pulmonary goblet cell hyperplasia. In OVA323–339-immunized mice, AHR and goblet cell hyperplasia were noted, with little eosinophilia and parenchymal inflammation. The latter finding provides evidence for dissociating AHR from eosinophilia. In both cases mediastinal node hypertrophy occurred, and high levels of Th2 cytokines were produced by the lung and mediastinal lymph node cells (LNC). Interestingly, mediastinal LNC also produced high levels of Th1 cytokines. Lung cells produced much less Th1 cytokines than these LNC. These results demonstrate that DC when introduced i.t. are potent in inducing asthma-like diseases by recruiting lymphocytes to the lung-draining lymph nodes and by stimulating Th2 responses and also suggest that the lung environment strongly biases T cell responses to Th2.

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P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver

Cited by 73 publications

References 47 publications

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Neutrophil depletion protects against murine acetaminophen hepatotoxicity

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

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